Calcium pyrophosphate dihydrate (CPPD) deposition disease is characterized by CPPD crystal deposits in articular and fibrocartilage, especially knee minisci. The pathogenesis of cartilage degeneration in this arthritic disease is thought to include an amplification loop; damaged cartilage is predisposed to CPPD crystal deposition which in turn enzymatically or mechanically further damages the cartilage. This research proposal details studies which will use in vitro crystal growth model systems to assess the effect of collagen and the effect of whole meniscus fibrocartilage on the formation and growth of CPPD crystals. We propose to purify type I collagen from rat tail tendons, to prepare gels of native-type collagen fibrils, and to use them in collagen controlled ca and pyrophosphate (PPi) ionic diffusion model systems for CPPD deposition. Ionic diffusion leading to crystal formation will be carried out in two ways: 1) Native collagen gels will be set so that high initial [Ca] (25 mM) at one end of the gel and high initial [PPi] (10 mM) at the other must undergo ionic diffusion before crystallizing at or near physiologic ionic concentrations. 2) CPPD crystallization in native collagen gels will also be studied using constant physiologic [Ca] and [PPi] ionic gradients. We propose to determine if CPPD crystallization is affected by collagen type. In addition to type I collagen isolated from rat tail tendons, we will also purify type II collagen from the sternal cartilage from lathyritic chicks. Using our model system, CPPD crystal growth in these types of collagen will be compared. Further, we propose to determine if CPPD crystals preferentially nucleate on collagen by comparing CPPD crystallization kinetics in the types I and II collagen gels to that in gels composed of biological gelatin, silica gel, and agar. We propose to monitor the role of the intact versus separated cartilage components on CPPD crystal formation and growth by allowing physiological [Ca] and [PPi] solutions to diffuse through and crystallize in intact menisci cores. We also propose to measure crystal turnover during CPPD crystal formation in intact menisci by injection of 45Ca into the growth medium and quantitation of both uptake and release of 45Ca as a function of time.